TY - JOUR
T1 - A Randomized Controlled Trial to Assess the Effect of Lidocaine Administered via Throat Spray and Nebulization in Patients with Refractory Chronic Cough
AU - Abdulqawi, Rayid
AU - Satia, Imran
AU - Kanemitsu, Yoshihiro
AU - Khalid, Saifudin
AU - Holt, Kimberley
AU - Dockry, Rachel
AU - Woodcock, Ashley A.
AU - Smith, Jaclyn A.
N1 - Funding Information:
This study was funded by a GlaxoSmithKline Investigator-led study grant. J.A.S. is funded by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre and a Wellcome Investigator Award (207504/B/17/Z) and is an NIHR Senior Investigator.Conflicts of interest: I. Satia reports a fellowship grant (Respire 3, European Union Co-Funded H2020) from the European Respiratory Society; speaker fees from GlaxoSmithKline (GSK) and AstraZeneca; and grants and personal fees from Merck Canada, outside the submitted work. A. A. Woodcock reports personal fees from GSK, Novartis, Chiesi, Axalbion, Reacta Biotech, and the Medicines Evaluation Unit, outside the submitted work, and is Chairman and has shareholding in Axalbion, a company developing a topical TRPM8 agonist for chronic cough. J. A. Smith has received grants from Merck, Ario Pharma, GSK, NeRRe Pharmaceuticals, Menlo, Bellus, and Bayer and personal fees from Chiesi, Ario Pharma, GSK, NeRRe Pharmaceuticals, Menlo, Bellus, Bayer, Boehringer Ingleheim, Genentech, and Neomed. A. A. Woodcock and J. A. Smith are named inventors on a patent, owned by Manchester University NHS Foundation Trust and licensed to Vitalograph Ltd, describing the detection of cough from sound recordings. The VitaloJAK cough monitoring algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd). MFT receives royalties that may be shared with the clinical division in which A. A. Woodcock and J. A. Smith work.We thank GlaxoSmithKline (GSK) for funding this study, and in particular Dr Robert Murdoch (GSK) who assisted with sourcing of the lidocaine therapy. This study was performed with the support of the National Institute for Health Research Manchester Clinical Research Facility.
Funding Information:
Conflicts of interest: I. Satia reports a fellowship grant (Respire 3, European Union Co-Funded H2020) from the European Respiratory Society; speaker fees from GlaxoSmithKline (GSK) and AstraZeneca; and grants and personal fees from Merck Canada , outside the submitted work. A. A. Woodcock reports personal fees from GSK, Novartis, Chiesi, Axalbion, Reacta Biotech, and the Medicines Evaluation Unit, outside the submitted work, and is Chairman and has shareholding in Axalbion, a company developing a topical TRPM8 agonist for chronic cough. J. A. Smith has received grants from Merck , Ario Pharma , GSK , NeRRe Pharmaceuticals , Menlo , Bellus , and Bayer and personal fees from Chiesi, Ario Pharma, GSK, NeRRe Pharmaceuticals, Menlo, Bellus, Bayer, Boehringer Ingleheim, Genentech, and Neomed. A. A. Woodcock and J. A. Smith are named inventors on a patent, owned by Manchester University NHS Foundation Trust and licensed to Vitalograph Ltd, describing the detection of cough from sound recordings. The VitaloJAK cough monitoring algorithm has been licensed by Manchester University Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd). MFT receives royalties that may be shared with the clinical division in which A. A. Woodcock and J. A. Smith work.
Funding Information:
This study was funded by a GlaxoSmithKline Investigator-led study grant. J.A.S. is funded by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre and a Wellcome Investigator Award (207504/B/17/Z) and is an NIHR Senior Investigator .
Funding Information:
We thank GlaxoSmithKline (GSK) for funding this study, and in particular Dr Robert Murdoch (GSK) who assisted with sourcing of the lidocaine therapy. This study was performed with the support of the National Institute for Health Research Manchester Clinical Research Facility .
Publisher Copyright:
© 2020 American Academy of Allergy, Asthma & Immunology
PY - 2021/4/7
Y1 - 2021/4/7
N2 - Background: Refractory chronic cough (RCC) is a debilitating condition for which there are no licensed treatments. Lidocaine is a nonselective inhibitor of voltage-gated sodium channels with potential antitussive effects, but randomized placebo-controlled studies evaluating its efficacy in RCC are lacking. Objective: To investigate the efficacy of nebulized lidocaine and lidocaine throat spray versus matched placebos in RCC. Methods: This was a randomized, double-blind, double-dummy, placebo-controlled, 3-way crossover study, comparing the effect of single doses of nebulized lidocaine with lidocaine delivered by a throat spray and matched placebo. The primary end point was cough frequency over the 10 hours following treatment. Secondary end points were visual analog scale scores for urge-to-cough and cough severity; an exploratory analysis evaluated hourly cough rates up to 5 hours after treatment. Results: Twenty-six subjects with RCC were recruited (22 females; mean age, 53.5 ± 12.1 years; FEV
1 %predicted, 105.2 ± 16.8 L; forced vital capacity %predicted, 112.4 ± 18 L). Lidocaine throat spray, but not nebulized lidocaine, significantly reduced 10-hour cough frequency as compared with placebo (throat spray, 22.6 coughs/h; nebulization, 26.9 coughs/h; and placebos, 27.6 coughs/h; P =.04,). Lidocaine throat spray showed the greatest effect on cough compared with placebo in the first hour after administration (31.7 coughs/h vs 74.2 coughs/h; P =.004). Both nebulizer and spray treatments significantly alleviated urge-to-cough and cough severity visual analog scale scores compared with placebo (P <.05). There were no serious adverse events associated with lidocaine therapy. Conclusions: Lidocaine throat spray was effective in reducing cough frequency in patients with RCC. Voltage-gated sodium channel inhibitors applied to pharynx have potential as therapies for RCC.
AB - Background: Refractory chronic cough (RCC) is a debilitating condition for which there are no licensed treatments. Lidocaine is a nonselective inhibitor of voltage-gated sodium channels with potential antitussive effects, but randomized placebo-controlled studies evaluating its efficacy in RCC are lacking. Objective: To investigate the efficacy of nebulized lidocaine and lidocaine throat spray versus matched placebos in RCC. Methods: This was a randomized, double-blind, double-dummy, placebo-controlled, 3-way crossover study, comparing the effect of single doses of nebulized lidocaine with lidocaine delivered by a throat spray and matched placebo. The primary end point was cough frequency over the 10 hours following treatment. Secondary end points were visual analog scale scores for urge-to-cough and cough severity; an exploratory analysis evaluated hourly cough rates up to 5 hours after treatment. Results: Twenty-six subjects with RCC were recruited (22 females; mean age, 53.5 ± 12.1 years; FEV
1 %predicted, 105.2 ± 16.8 L; forced vital capacity %predicted, 112.4 ± 18 L). Lidocaine throat spray, but not nebulized lidocaine, significantly reduced 10-hour cough frequency as compared with placebo (throat spray, 22.6 coughs/h; nebulization, 26.9 coughs/h; and placebos, 27.6 coughs/h; P =.04,). Lidocaine throat spray showed the greatest effect on cough compared with placebo in the first hour after administration (31.7 coughs/h vs 74.2 coughs/h; P =.004). Both nebulizer and spray treatments significantly alleviated urge-to-cough and cough severity visual analog scale scores compared with placebo (P <.05). There were no serious adverse events associated with lidocaine therapy. Conclusions: Lidocaine throat spray was effective in reducing cough frequency in patients with RCC. Voltage-gated sodium channel inhibitors applied to pharynx have potential as therapies for RCC.
KW - Lidocaine
KW - Refractory chronic cough
KW - Sensory afferents
KW - Voltage-gated sodium channels
U2 - 10.1016/j.jaip.2020.11.037
DO - 10.1016/j.jaip.2020.11.037
M3 - Article
SN - 2213-2198
VL - 9
SP - 1640
EP - 1647
JO - The Journal of Allergy and Clinical Immunology: In Practice
JF - The Journal of Allergy and Clinical Immunology: In Practice
IS - 4
ER -